The ability of islet transplantation to reproducibly reverse diabetes for extended periods has been demonstrated in recent clinical studies. However the need for 2-3 donor organs per transplant means that less than 1% of the insulin-dependent diabetes (IDDM) population could be treated with this protocol. The ultimate objective of this proposal is focused on the identification and expansion of progenitor cells from adult pancreas that can be used in the development of cell therapies for multiple patients from a single pancreas donation. The Company has obtained an exclusive license to culture methods developed by Dr. Parenteau (Amaranth Bio, Inc.) and Dr. Rosenberg (McGill University) for obtaining endocrine progenitor cells. This proposal is a feasibility study to determine the commercial reality of this technology. The research proposal is divided in to three specific aims employing human pancreas-derived cells; 1) Verification that the licensed culture methodology results in the production of islet-like, dithizone positive clusters of progenitor cells from adult human pancreas; 2) Assessment of the differentiation potential of human endocrine progenitor cells by implantation beneath the renal kidney capsule in immunodeficient, diabetic mice. The recipients will be evaluated for the appearance of human C-peptide, human insulin, changes in blood glucose levels, and by immunohistochemical evaluation of the explanted implant site; and 3) Demonstration of human pancreatic endocrine progenitor cell expansion to a level appropriate for treatment of multiple patients with retention of progenitor markers (including Ngn3 and Pdx1) and the ability to form dithizone positive islet-like structures. Successful demonstration of feasibility in these Phase I SBIR studies will consist of technology transfer verification in Specific Aim #1, demonstration of functional human [unreadable] cells in Specific Aim #2, and expansion of individual cell strains to numbers anticipated to be required for at least 3-10 patients in Specific Aim #3. These results would provide the basis for follow-on Phase II SBIR studies designed to assess product safety, and optimize production for use of these progenitor cells in the commercial development of a Type 1 diabetes cell therapy. Approximately 1.6 million people are insulin-dependent. Type I (usually juvenile-onset) insulin-dependent diabetes mellitus (IDDM) results from autoimmune damage and subsequent loss of the islet beta ([unreadable]) cells. Islet cell transplantation has recently been shown to be an effective treatment but there is only a very limited source of cells. The progenitor cell expansion technology prospectively fulfills unmet clinical needs by supplying a source of [unreadable] cells. Multiple transplants may be performed from single pancreas donations resulting in cost savings due to removal of patients from chronic dialysis, reduction of diabetes associated morbidity, and the transition of islet transplantation from an emergency procedure to an elective procedure. [unreadable] [unreadable] [unreadable]